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Scottish Colorectal Cancer Vitamin D Intervention Study (SCoViDS)

ABSTRACT: Scottish Colorectal Cancer Vitamin D Intervention Study (SCoViDS)

PROVIDER: PRJNA663581 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12643500_1.fastq.gz	Fastqsanger.gz
	SRR12643500_2.fastq.gz	Fastqsanger.gz
	SRR12643600_1.fastq.gz	Fastqsanger.gz
	SRR12643600_2.fastq.gz	Fastqsanger.gz
	SRR12643700_1.fastq.gz	Fastqsanger.gz

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Scottish Colorectal Cancer Vitamin D Intervention Study (SCoViDS) [RNA-seq]

Project description:Scottish Colorectal Cancer Vitamin D Intervention Study (SCoViDS) [RNA-seq]

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Vitamin D receptor expression and associated gene signature in tumor stromal fibroblasts predict clinical outcome in colorectal cancer

Project description:Colorectal cancer (CRC) is a major cause of cancer mortality and a serious health concern worldwide. Vitamin D deficiency is associated with high CRC incidence and mortality, suggesting a protective effect of vitamin D against this neoplasia. Although the antiproliferative and prodifferentiation action of active vitamin D (1alpha,25-dihydroxyvitamin D3, 1,25(OH)2D3) on colon carcinoma cells is well documented, its potential effects on CRC stroma are unknown. Here, we show that high vitamin D receptor (VDR) expression in tumor stromal fibroblasts is associated with better overall and progression-free survival in a large cohort of CRC patients, irrespective of its expression in carcinoma cells. Consistently, 1,25(OH)2D3 inhibits the activation of patient-derived normal and cancer-associated fibroblasts, and their pro-migratory effect on carcinoma cells. Importantly, we show by global transcriptomic analyses that 1,25(OH)2D3 regulates cancer-associated fibroblast gene expression and imposes a gene signature that is associated with longer overall and disease-free survival of CRC patients. Moreover, expression of two genes from the signature, CD82 and S100A4, correlates with stromal VDR expression and clinical outcome in CRC. This study provides the first evidence that vitamin D has protective effects against CRC through the regulation of stromal fibroblasts. Characterization of 1,25(OH)2D3 action on gene expression in primary cultures of colon normal and tumor fibroblasts established from samples from colorectal cancer patients. RNA from seven paired normal and tumor fibroblast primary cultures treated with 1,25(OH)2D3 or vehicle for 48 h were analyzed.

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